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时间同步、异时性和节律障碍:人类昼夜节律的内部不同步是疾病的征兆吗?

Euchronism, allochronism, and dyschronism: is internal desynchronization of human circadian rhythms a sign of illness?

作者信息

Reinberg Alain E, Ashkenazi Israel, Smolensky Michael H

机构信息

Unité de Chronobiologie, Fondation A. de Rothschild, 29 rue Manin, 75940 Paris Cedex 19, France.

出版信息

Chronobiol Int. 2007;24(4):553-88. doi: 10.1080/07420520701534624.

DOI:10.1080/07420520701534624
PMID:17701673
Abstract

The authors define a subject as euchronic when the circadian parameters--tau (tau=period), Ø (acrophse or peak time), A (amplitude), and M (MESOR=24 h rhythm-adjusted mean)--of a set of circadian variables are within the confidence limits of appropriate reference values of healthy subjects (HS). We define internal desynchronization as a state in which the circadian tau of a set of rhythms differs from 24 h and when the tau of a given variable differs from that of other variables. Such a state was first observed in singly isolated HS without access to time cues and clues. Herein, data and analyses are presented demonstrating that internal desynchronization appears to be a rather common phenomenon in HS dwelling in their natural environment (i.e., in the presence of usual zeitgebers). This has been documented by longitudinal studies (n approximately=15 days) of the circadian rhythm in sleep-wakefulness, body temperature, right- and left-hand-grip strength, and reaction time involving a total of 246 HS and 134 shift workers (SW), with 45.5% showing good and 54.5% poor SW tolerance. The presence of internal desynchronization observed in SW was associated SW intolerance, with symptoms being sleep alteration/disturbances, sleeping-pill dependence, persisting fatigue (asthenia), mood alteration, and digestive complaints. Internal desynchronization was also documented in groups of HS and tolerant SW, though it was almost the rule among the intolerant SW. The authors introduce two new terms: allochronism to describe the time organization of those SW who evidence internal desynchronization without detectable clinical symptoms, and dyschronism to describe the time organization of those SW who exhibit internal desynchrobization plus the symptoms of SW intolerance or medical illness. The condition of allochronism is not restricted only to SW tolerance, as it was detected in 112 HS without medical complains when exposed to various experimental conditions, including medications and placebos, sojourn in the high Arctic summer, intensive sport training, and task-loaded cognitive performance testing. Dyschronism in SW who are sleep-deprived is associated with persisting fatigue. An unpublished Gallup survey found that 47% of 2478 respondents experienced a state of asthenia during the previous 12 months, with symptoms mimicking those of SW intolerance. In one-third of the cases, the origin of the asthenia was undetermined. Taking into account the high incidence of internal desynchronization found in past investigations and the clinical observation that sleep deprivation is a consequence of many acute and chronic medical conditions (nocturnal pain, nocturnal asthma, etc.), it is suggested that dyschronism may be responsible for the asthenia of unknown origin, at least for some persons. The interindividual (including sex-related) variability in the propensity to exhibit an altered temporal organization, whether it be transient or persistent (i.e., reversible or non-reversible) suggests the involvement of genetic factors. The Dian-Circadian genetic model previously proposed by the authors seems pertinent to conceptualize and explain the various levels and output of internal desynchronization.

摘要

作者将一组昼夜节律变量的昼夜节律参数——τ(τ=周期)、ø(相位或峰值时间)、A(振幅)和M(MESOR=24小时节律调整均值)——处于健康受试者(HS)适当参考值的置信区间内的个体定义为节律正常。我们将内源性失同步定义为一组节律的昼夜节律τ不同于24小时,且给定变量的τ与其他变量的τ不同的状态。这种状态最初是在没有时间线索的单独隔离的HS中观察到的。在此,我们展示了数据和分析结果,表明内源性失同步在自然环境中居住的HS中似乎是一种相当常见的现象(即在存在通常的昼夜节律授时因子的情况下)。这已通过对睡眠-觉醒、体温、右手和左手握力以及反应时间的昼夜节律进行的纵向研究(约15天)得到证实,该研究共涉及246名HS和134名轮班工作者(SW),其中45.5%的SW耐受性良好,54.5%的SW耐受性较差。在SW中观察到的内源性失同步与SW不耐受相关,症状包括睡眠改变/干扰、安眠药依赖、持续疲劳(乏力)、情绪改变和消化问题。在HS组和耐受性良好的SW组中也记录到了内源性失同步,尽管在不耐受的SW组中几乎是常态。作者引入了两个新术语:异时性,用于描述那些表现出内源性失同步但无明显临床症状的SW的时间组织;节律失调,用于描述那些表现出内源性失同步并伴有SW不耐受症状或疾病的SW的时间组织。异时性状态不仅限于SW耐受性,因为在112名无医学主诉的HS中也检测到了这种状态,这些HS暴露于各种实验条件下,包括药物和安慰剂、在北极夏季停留、高强度运动训练以及任务负荷认知性能测试。睡眠不足的SW中的节律失调与持续疲劳有关。一项未发表的盖洛普调查发现,在2478名受访者中,47%的人在过去12个月中经历过乏力状态,症状类似于SW不耐受。在三分之一的病例中,乏力的原因未确定。考虑到过去调查中发现的内源性失同步的高发生率以及睡眠剥夺是许多急性和慢性疾病(夜间疼痛、夜间哮喘等)的后果这一临床观察结果,有人提出节律失调可能是不明原因乏力的原因,至少对某些人来说是这样。个体间(包括与性别相关的)在表现出时间组织改变的倾向方面的变异性,无论是短暂的还是持续的(即可逆的或不可逆的),都表明遗传因素的参与。作者先前提出的Dian-昼夜节律遗传模型似乎与概念化和解释内源性失同步的各个层面和输出相关。

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